title: Asymmetric synthesis and catalytic activity of 3-methyl-β-proline in enantioselective anti-Mannich-type reactions.
abstract: Enantiomerically pure 3-methyl-β-proline was synthesized using an asymmetric phase-transfer-catalyzed alkylation of a cyanopropanoate to establish the all-carbon stereogenic center. The catalytic activity of 3-methyl-β-proline in the Mannich-type reaction between a glyoxylate imine and ketones/aldehydes was subsequently investigated. The catalyst was designed and found to be more soluble in nonpolar organic solvents relative to the unsubstituted β-proline catalyst, and as a result allowed for added flexibility during optimization efforts. This work culminated in the development of a highly anti-diastereo- and enantioselective process employing low catalyst loading.
authors.affiliation: School of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nagata
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kuga
authors.forename: Akinori
authors.initials: A
authors.lastname: Higashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kinoshita
authors.forename: Takuya
authors.initials: T
authors.lastname: Kanemitsu
authors.forename: Michiko
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Itoh
mesh_terms: D000478:Alkylation; D002384:Catalysis; D015394:Molecular Structure; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D011407:Propane / Q000031:analogs & derivatives / Q000737:chemistry*
chemical_list: D011392:Proline; D011407:Propane